Mercury compounds and process of preparing same



Patented May 31, 1949 MERCURY COMPOUNDS AND PROCESS OF PREPARING SAMEMax Hartmann and Werner Bosshard, Riehen, Switzerland, assignors to CibaPharmaceutical Products Inc., Summit, N. J., a corporation of New JerseyNo Drawing. Application June 30, 1945, Serial No. 602,676. InSwitzerland August 4, 1944 14 Claims. 1

The present invention relates to the manufacture of new mercurycompounds of the formula and their use in disinfectant preparations. Inthis formula R stands for alkyl, cycloalkyl or aryl univalenthydrocarbon radicals, such as methyl, ethyl, propyl, ethoxyethyl,methylcyclohexyl or phenyl, R1 stands for alkylene, aralkylene orarylene divalent hydrocarbon radicals, such as ethylene, propylene,phenylenmethylene or phenylene, R2, R3 and R4 stand for alkyl, such asmethyl, ethyl or propyl. A stands for the radical of an alkyl-sulfuricacid, or aryl-sulfonic acid. There may especially be mentioned, forexample, ethylmercurithioethyl-trimethyl ammonium methosulfate,ethylmercurithioethyl-dlethyl methylammonium-methosulfate,propylmercurithioethyl-trimethyl-ammonium methosulfate,dodecylmercurithloethyl-trimethyl ammoniurnmethosulfate,propylmercurithioethyl-diethyl-methylammonium-methosulfate,ethylmercurithioethyltrimethyl ammonium para toluenesulfonate,ethylmercurithioethyl-dimethyl-ethyl ammoni um-ethosulfate,phenylmercurithioethyl-trimethyl-ammonium-methosulfate andethylmercurithiophenyl-trimethyl-ammonium-methosulfate.

The new mercury compounds can be obtained byulquaternatingmercurithioamines of the form a wherein R, R1, R2 and R3 have the aboveindicated significance, or causing organic mercury hydroxides or saltsto react with corresponding quaternary thioammonium salts.

As quaternating agents there can be used dialkylsulfates such asdimethylsulf ate or diethylsulfate, or arylsulfonic acid esters such asparatoluenesulfonic acid methylester. The reactions are advantageouslycarried out in the presence of solvents such as alcohol. In case themereurith oamines u d as sta t n mater als, for example, thealkyl-mercurithioalkylamines, are not known, they can be obtained byreaction of alkylmercury hydroxides or salts with thioamines such asthioalkylamines, for exam le, with aminoallnrlmercaptans ordi-aminoalkyl-disulfides. The preparation of these startina materials isadvantageously conducted in alcohol in the 2 presence of alkalies. Thequaternary thioammonium salts used as starting materials are obtained bytreating thioamines with quaternating agents.

It was not to be expected that the present process could be carried out,for it is surprising that the mercurithioamines are not split by theaction of the quaternating agents. Thus, it had become known from G.Sachs (Annalen der Chemie, vol. 433, page [1923]) that splitting of themolecule occurs in the reaction of phenylmercurithioethane withethyliodide or benzyliodide.

The mercurithioammonium salts obtained according to the present processare readily soluble in water. They have excellent disinfectingproperties and are therefore to be used as disinfectant preparations.Thus, for example, ethylmercurithioethyl-trimethyl-ammonium-methosulfateexhibits considerably better disinfecting values when tested onbacterium coli and pseudomonas pyocyaneus than quaternary ammonium saltsor mercury compounds which are known as disinfectants.

The new disinfectant preparations are suitable for a very wide range ofapplications. Thus, they are suitable for disinfecting the skin, forexample, the hands, and also instruments, bandage material, washes,sputum and the like. They may be used, for example, in the form of asolution, or a salve or powder. It has been found of advantage to admixtherewith other compounds having a disinfecting action. As suchadditions there may be used, for example, the above indicated tertiarymercurithioamines or quaternary ammonium salts which are free frommercury, such as quaternary quinolyloxyalkylor phenoxyalkylammoniumcompounds. There may be mentioned, for exam le,[p3-(5:7-dichloro-quino1yl- (8) -oxy) -ethyl]-dimethyl dodecyl ammoniumbromide, [,8-(5z7-dichloro quinolyl (8) oxy)ethyl]-dimethyl-hexadecyl-ammonium bromide, [[3- (2-methy1-5:7dlchloro-quinolyl (8) oxy) ethyl]-dimethyl-dodecylammonium bromide,flphenoxyethyl dimethyl dodecyl ammonium chloride or bromide,fl-phenoxyethyl-dimethylhexadecyl-ammonium bromide,fl-(para-chlorophenoxy) -ethyl-dlmethyl dodecyl ammonium bromide,B-(para-methyl phenoxy) ethyl di methyl dodecyl ammonium bromide and B(para-tertiary octyl'ohenoxy) ethyl dimethyl dodecyl-ammonium bromide.These compounds are obtained. for exam e. by caus n quater atns! a entsto act on ouino lor nhenvl-o va kvlamines. With the aid of thesemixtures disinfectant preparations are obtained which have more valuableproperties than the individual components.

The following examples illustrate the invention, the parts being byweight unless otherwise stated and the relationship of parts by weightto parts by volumebeing the same as that of the kilogram to the liter:

Example 1 16 parts of a mixture of ethyl mercury chloride and bromideare suspended in 150 parts by volume of alcohol and boiled for 20minutes after addition of 5 parts by volume of N-caustic soda solution.When cold, the mixture is filtered and the filtrate poured into asolution of dimethylaminoethylmercaptanprepared by reaction of 7.5 partsof dimethylaminoethylmercaptan-hydrochloride in '70 parts by Volume ofalcohol by addition of 5 parts by volume of 10 N-caustic soda solutionand filtering in the cold. This solution is boiled for I hour underrefiux,-the alcohol is distilled oif and the residuetakenup in ether.Afterf distilling the ether. parts of the eylmerc'i'irithioethyl-'dimethylarnine remain behind as alight oil-whichboils with weak decomposition at 124- C. under a ressu e of 0.1 Hg; itcan also be distilled with steam.

The same compound can also be obtained in the fol owing manner:

31 parts of a mixture of 'ethvl mercury chloridea'nd bromide areintroduced into 140 parts by volume of alcohol containing 2 6, partsofdissolved sodium. Further. 15 partsof'bis-dimethylaminoetbyl-d'isulfide hydrochloride are introduced into140 parts by volume of alcohol containing 2.3 parts of dissolved sodium.and the whole is filtered. The filtrate is added to the above solut onof the ethyl mercury hydroxide and boiled for 1 hours under reflux. Theproduct is worked up as described above and 29 parts of the said mercurythioamine compound are thus obtained.

15, parts of the ethylmercurithioethyl-dimethyl amine are taken up in 40parts by volume of absolute alcohol, the solution is mixed with 4.4parts by-volume of dimethylsulfate and the alcohol is distilled on thewater-bath after the reaction is complete. The residue is treated withether. The ethylmercurithioethyl-trimethyl-ammonium-methosulfateinsoluble in ether is left behind. Aqueous solutions of any desiredconcentration may be prepared therefrom.

If instead of 16 parts of a mixture of ethyl mercury chloride andbromide there are used 225 parts of dodecyl mercury bromide, thedodecylmercurithioethyl-trimethyl-ammonium methosulfate is obtained. ananalogous manner.

100 parts of ethylmercurithioethyl trimethylammonium-methosulfate' aremade up with water to 1000 parts by volume, if desired with the additionof odoriferous substances. When appropri ately diluted, such a solutioncan be used as a sinf ctin p p a The following solutions possessparticularly adv n ageous prope i 100 parts of an aqueoussolution of 0.2per cent, strength of ethylmercurithioethyl-trimethylammoniumrmethosulfate are mixed with 50, 100 or zllflparts ofan aqueous solution of 0.2 per cent. strength of.B-phenoxyethyl-dirnethyl-dodecyl-, ammoniumbromide (obtained, forexample, by heating o=phenoxyethyl-dimethy1amine with dodefiylbromide) Iartsof an-aqueoussolution of 1 perc n 4 strength ofethylmercurithioethyl-trimethyl-ammonium-methosulfate are introduced,while stirring, into 50 parts of an aqueous solution of 1 per cent.strength of B-phenoxyethyl-dimethyldodecy1 =amm0nil mmi e-- A solutionof 3 per cent. strength of the above mentioned compounds can be preparedin a similar manner with alcohol of 50 per cent. strength.

Example 2 10 parts of the i.ethylmercurithioethyl-di-.methylamineoobtained according to Example 1 -n'a't'e.--isobtained byworking in an analogous manner.

dr chtlo ide are d ssolv d in 70" parts y vjo' u oi alcohol and mixedwith 1 equivalent of 10 N-caustic soda solution. The mixture is filteredand 5 parts by volume of .dimethyl'sulfate are added. After evaporationof the alcohol and extraction with ether, 10 parts ofmercaptoethyltrimethyleammonium methosulfate behind.

2.3 partsofthis methoSulfate are dissolved in 50parts-byvolume ofalcohol and caused to' react'with the ethyl. mercury hydroxide obtainedfrom 3.1' parts ot a mixture of the ethylmercury chloride andbromid'eaccording to Example 1 by boiling for 1 hour under'reflux. The mixtureis filtered wheriflcol'd, the filtrate is evaporated to dryness, theresidue is taken up in water" and filtered, and theethylmercurithioethy1=trimsthylammonium methosulfate described in'Example 1 is thus obtained.

Example 4 3. 1-:-parts :of ethyl mercury bromide are= suspended inlOGa-partsfof alcohol, mixed with 1;? parts of-diethyiaminoethylmercaptan hydrochloride and-3 parts by volume of 10 Ncaustic soda solution and boiled for one "hour" under reflux. When:cold,xthe'm-ixture is filtered-, worked up ase'describedin Example 1 and3.1 parts-oi the ethylmercurithioethyl-diethylamine are thus obtained.

3.1 parts-pf-thismercury compound-are dissolved in 20 parts by volume ofalcohol, 0.86 part by volume of dimethylsulfate is added thereto and theproduct worked up as described in Example 1.

-3.7 parts of theethylmercurithioethyl-diethylmethyl-ammonium-methosulfate are thus obad.

l palt of ethylmercurithioethyl-diethyl-methyl-ammonium-rnethosulfate isdissolved in 10 a parts of alcohol of 70 per cent. strength by volume,ifdesired withthe-addition of coloring and odoriierous substances, Atincture is thus obtained which has a good disinfecting action.

Ewamme 5 hydrochloride. 2.4 parts of, the n propylmercurithioethyl-dimethylamine are thus obtained.

2.4 parts of this mercury compound can be reacted WithOJ T part byvolume of dimethylsulfate are left Example 6 3.25 parts of a mixture ofn-propyl mercury chloride and bromide are worked up according to Example1 and reacted with 1.7 parts of diethylaminoethylmercaptan-hydrochlorideas described in Example 5. 2.8 parts ofn-propyl-mercurithioethyldiethylamine are thus obtained.

These 2.8 parts of the mercury compound are caused to react with 0.;part by volume of dimethylsulfate to form then-propylmercurithioethyl-diethylmethyl-ammonium-methosulfate.

Example 7 6.6 parts of phenylmercury acetate in 250 parts by volume ofalcohol are caused to react with 2 parts by volume of 10 N-caustic sodasolution during 30 minutes on the water-bath, and filtered when cold.The filtrate is mixed with a solution of 2.2 parts ofdimethylaminoethylmercaptan in alcohol and the alcohol is distilled ofion the water-bath. The residue is taken up in alcohol and filtered. Thephenylmercurithioethyldimethylamine is crystallized from the solution;it melts at 105-106 C. after recrystallization from alcohol.

5 parts of the obtained phenylmercurithioethyldimethylamine in 5 partsof alcohol are reacted on the water-bath with 1.35 parts by volume ofdimethylsulfate. After distilling off the alcohol thephenylmercurithioethyl-di-- methyl-ammonium-methosulfate is left behindwhich is readily soluble in water.

For example, the following solution having a disinfecting action can beprepared:

50 parts of an aqueous solution of 0.1 per cent. strength ofphenylmercurithioethyl-trimethyl-ammonium-methosulfate are introducedinto 50 parts of an aqueous solution of 0.1 per v Example 8 6.2 parts ofethyl mercury bromide are caused to react with caustic soda solution asdescribed in Example 1 and the filtered solution is mixed with analcoholic solution of 2.6 parts of paramercapto-dimethylaniline. Thepara-ethylmercurithio-dimethylaniline is precipitated in crystallineform after heating for a short time. After recrystallizing from alcoholthe base melts at 80 C. and is insoluble in water. 3.8 parts of thepara-ethylmercurithio-dimethylaniline are dissolved in little alcoholand mixed with 1 part by volume of dimethylsulfate. The aicohol isdistilled off on the water-bath and there is thus obtained thepara-ethylmercurithiophenyl-tri-- methyl-ammonium-methosulfate which isfreely soluble in water. After recrystallization from a mixture ofmethyl alcohol and acetic ester the product melts at 125 C.

This compound can be pressed into tablets in the following manner:

1 part of para-ethylmercurithiophenyl-trimethyl-ammonium-methosulfate ispressed into tablets with 10-50 parts of starch, sugar or urea orsimilar inert products.

What we claim is:

1. Mercury compounds of the formula wherein R is a member selected fromthe group consisting of alkyl, cycloalkyl and aryl univalent hydrocarbonradicals, R1 is a member selected from the group consisting of alkylene,aralkylene and arylene divalent hydrocarbon radicals, each of R2, R3 andR4 represents an alkyl univalent hydrocarbon radical, and A is an anionselected from the group consisting of alkyl sulfate ions and arylsulfonate ions.

2. Alkylmercurithioalky trialkyl ammoniumalkyl-sulfates.

3. Phenylmercurithioalkyl trialkyl ammonium-alkyl-sulfates.

4. Alkylmercurithiophenyl trialkyl ammonium-alkylsulfates.

5. Ethylmercurithioethyl trimethyl-ammonium-methosulfate.

6. Phenylmercurithioethyl-trimethyl-ammonium-methosulfate.

7. Ethylmercurithiophenyl-trimethyl-ammonium-methosulfate.

8. Process for the manufacture of a mercury compound comprising treatinga mercurithioamine of the formula wherein R is a member selected fromthe group consisting of alkyl, cycloalkyl and aryl univalent hydrocarbonradicals, R1 is a member selected from the group consisting of alkylene,aralkylen and arylene divalent hydrocarbon radicals, and each of R2 andR3 represents an alkyl univalent hydrocarbon radical, with an ester ofthe formula RA-A wherein R4 represents an alkyl univalent hydrocarbonradical and A is an anion selected from the group consisting of alkylsulfate ions and aryl sulfonate ions.

9. Process for the manufacture of a mercury compound comprising reactingan alkylmercurithioalkyl-dialkylamine with a dialkylsulfate.

10. Process for the manufacture of a mercury compound comprisingreacting a phenylmercurithioalkyl-dialkylamine with a dialkylsulfate.

11. Process for the manufacture of a mercury compound comprisingreacting an alkylmercuri thiophenyl-dialkylamine with a dialkylsulfate.

12. Process for the manufacture of a mercury compound comprisingreacting ethylmercurithioethyl-dimethylamine with dimethylsulfate.

13. Process for the manufacture of a mercury compound comprisingreacting phenylmercurithioethyl-dimethylamine with dimethylsulfate.

14. Process for the manufacture of a mercury compound comprisingreacting ethylmercurithiophenyl-dimethylamine with dimethylsulfate.

MAX I-IARTMANN. WERNER BOSSHARD.

(References on following page) REFERENCES CITED FOREIGN PATENTS Thefollowing references are of record in the Number Country Date file ofthis patent: 199,452 Switzerland Aug. 3.1, .1938

UNITED STATES PATENTS 5 OTHER REFERENCES Numb r Na D t Rawlins et aL,Jr. of the Amer. Pharm. Assoc.

1,672,615 Kharasch June 5, 1928 0 3 3, pa es 11 t0 6. 2,060,850 CalcottNov. 17, 1936 Sidgwicks Organic Chemistry of .Nitrogen; 2,087,131 TaubJuly 13, 1937 10 1937, pgs. 27, 28 and 29.

2,129,376 Kharasch Sept. 6, 1938 Certificate of Correction Patent No.2,471,622. May 31, 1949.

MAX HARTMANN ET AL. It is hereby certified that error appears in theprinted specification of the above numbered patent requiring correctionas follows:

Column 3, line 32, for 2 6 parts read 2.6 parts;

and that the said Letters Patent should be read with this correctiontherein that the same may conform to the record of the case in thePatent Ofiice.

Signed and sealed this 1st day of November, A. D. 1949.

THOMAS F. MURPHY,

Assistant Oommz'ssz'oner of Patents.

